A chronic destructive arthritis emerges 10-14 days after i.v. infection with 5 by 10 to the 5th power live Salmonella enteritidis/100 g of body weight in 70 percent of adult rats. The distribution and pathology of the joint lesions bear resemblances to human rheumatoid arthritis. This Salmonella-associated arthritis (SAA) can be simulated by injecting large numbers of heating-killed (but not living) S. enteritidis directly into the joints of specifically immunized rats. This observation and the fact that only 2-6 percent of immature rats (weanling) and thymusdeprived rats develop SAA strongly suggest that the joint damage in SAA is an immunologically mediated process. It is proposed to determine the precise immunological interactions that lead to the development of destructive arthritis by selectively transferring in turn, functional T-cells, B-cells and macrophage precursors to restore the capacity for the development of SAA in deficient rats in addition to the converse procedures of selective immunological impairment of function of T-cells, B-cells and complement. The fate and function of Salmonella antigens following intra-articular or IV injections will be studied by means of radiotracing and immunofluorescence in immune and naive hosts. THe immunological responses in immature rats and adults will be evaluated by concommitantly measuring T-cell functions, alterations in immunoglobulins. Monospecific antisera will be prepared to identify and quantitate Ig subclass responses. Antigenically defined Salmonella species will be tested for arthritogenic potential. Related and unrelated antigens also will be assessed for this potential. Additional assessments will involve the role of C', immune complexes in joints and serum and the presence of anti-globulins. The results of these investigations should help resolve problems related to the pathogenesis of human rheumatoid arthritis and contribute to the understanding of immunological maturation in children.